DESCRIPTION (Investigator's Abstract): Characterization of the anatomical and functional organization of the mammalian circadian timing system (CTS) is the overall objective of this project. There are three main components of the CTS to be studied: (a) pacemakers that generate circadian signals, (b) entrainment pathways that modulate the period and phase of the pacemakers and (c) output pathways that couple the pacemaker to effector systems under circadian control. One Specific Aim is put forth for each of these components and studies are outlined that are directed at advancing understanding within each of these three broad categories. Proposed sutdies of entrainment pathways will further characterize the retinal ganglion cells (a) that project in the retinohypothalamic tract (RHT) to the suprachiasmatic nucleus (SCN) and other CTS-related areas and (b) those that project to areas innervated by SCN neurons, in contrast to those that project to other retinorecipient regions. Additional studies will analyze the substance P (SP) innervation of the SCN and the intergeniculate leaflet (IGL). Whether circadian oscillators are distributed throughout the SCN or are only characteristic of certain cell types in certain subdivisions will also be analyzed in transplant and explant culture studies. Since lesions that destroy the Nissl- defined SCN do not always eliminate all rhythms, planned studies will test the hypothesis that the functional clock extends beyond the boundaries of the SCN. Studies of the output of the CTS will characterize the organization and afferent connections of the subparaventricular zone. Possible roles of the SCN in influencing the activity of areas it innervates will be studied in slices, in vitro. Electrolytic and knife-cut lesions will be used in an attempt to test the hypothesis that specific groups of SCN efferents control particular circadian functions.